Abstract 4732
Background
The use of progesterone receptor (PR) ligands for adjuvant breast cancer treatment remains controversial. We propose that antiprogestins inhibit the breast tumor growth with high isoform A (PRA)/isoform B (PRB) ratio while progestins may inhibit those with opposite ratios.
Methods
We used metastatic models with different PR isoform ratios to evaluate the effect of antiprogestins [mifepristone (MFP), aglepristone (AGLE), telapristone acetate (TLP), ulipristal acetate (UPA), or progestins [medroxyprogesterone acetate (MPA) or progesterone (Pg)]. Murine BALB/c tumors with PRA>PRB (C7-2-HI) and PRB>PRA (C7-HI), human MDA-MB-231 cells transfected with PRB and the inducible MDA-MB-231-iPRAB cells were inoculated into NSG mice.
Results
All antiprogestins inhibited C7-2-HI tumor growth rate (MFP 88%, TLP 59% UPA 70%) and the onset of lymph node and lung metastasis. AGLE induced complete tumor regression. The progestin MPA, increased tumor size and metastasis in a 60% (p < 0.001) and Pg showed a similar trend (22%). MFP and AGLE also inhibited the tumor growth and number of metastatic foci of the MDA-MB-231-iPRAB expressing PRA. Onset of long-term metastasis was evaluated by tumor surgery after interruption of MFP or AGLE neoadyuvant treatment. Both antiprogestins increased the Disease Free Survival rate (p < 0.001) compared with controls. Six out of 8 and 3/5 mice receiving AGLE and MFP, respectively, are disease free one year after surgery. AGLE adjuvant treatment, also inhibited long-term metastasis (p < 0.001). With C7-HI model (PRB>PRA), AGLE, UPA or MFP increased tumor growth and/or metastasis (p < 0.001) whereas MPA showed an opposite trend in the number of metastatic foci. Experiments performed with the MDA-MB-231 cells transfected with or induced to express PRB confirmed the inhibitory effects of MPA on the metastatic development.
Conclusions
Progestins/antiprogestins stimulate or inhibit, respectively tumor growth/metastasis of mammary carcinomas with high PRA/PRB ratio, and they may exert opposite effects in tumors with low PRA/PRB ratio. These findings highlight the relevance of evaluating PR isofor.m ratio prior to PR ligand treatment on human breast cancer.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
CONICET.
Funding
CONICET; INC, ANPCYT.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
2672 - Changes in clinico-pathological characteristics of vulvar cancer in Japan: increasing oldest-old, stage-shifting, and decreasing cohort-level survival
Presenter: Shin Nishio
Session: Poster Display session 2
Resources:
Abstract
4306 - Tumor Treating Fields (200 kHz) concomitant with weekly paclitaxel for platinum-resistant ovarian cancer: Phase 3 INNOVATE-3/ENGOT-ov50 study
Presenter: Ignace Vergote
Session: Poster Display session 2
Resources:
Abstract
5136 - Randomized, phase 1b/2 study of M6620 + avelumab + carboplatin vs standard care (sc) in patients (pts) with platinum-sensitive poly (ADP-ribose) polymerase inhibitor-(PARPi)-resistant ovarian cancer
Presenter: Susana Banerjee
Session: Poster Display session 2
Resources:
Abstract
2296 - An umbrella study of biomarker-driven targeted therapy in patients with platinum-resistant recurrent ovarian cancer: A Korean Gynecologic Oncology Group study (KGOG 3045), AMBITION
Presenter: Jung-Yun Lee
Session: Poster Display session 2
Resources:
Abstract
2732 - A phase 2 study of pembrolizumab in combination with doxorubicin in advanced, recurrent or metastatic endometrial cancer
Presenter: Ana Oaknin
Session: Poster Display session 2
Resources:
Abstract
4404 - ENGOT-EN9/LEAP-001: a phase 3, randomized, open-label study of pembrolizumab plus lenvatinib versus chemotherapy for first-line treatment of advanced or recurrent endometrial cancer
Presenter: Christian Marth
Session: Poster Display session 2
Resources:
Abstract
4564 - Phase 1/2 trial of tisotumab vedotin plus bevacizumab, pembrolizumab, or carboplatin in recurrent or metastatic cervical cancer (innovaTV 205/ENGOT-cx8)
Presenter: Ignace Vergote
Session: Poster Display session 2
Resources:
Abstract
4933 - Updated data of Epitopes-HPV02 trial and external validation of efficacy of DCF in prospective Epitopes-HPV01 study in advanced anal squamous cell carcinoma. Pooled analysis of 115 patients
Presenter: Stefano Kim
Session: Poster Display session 2
Resources:
Abstract
2301 - Pre-specified pilot analysis of a randomised pilot/phase II/III trial comparing standard dose vs dose-escalated concurrent chemoradiotherapy (CRT) in anal cancer (PLATO-ACT5)
Presenter: Alexandra Gilbert
Session: Poster Display session 2
Resources:
Abstract
5773 - A prospective study of diffusion-weighted magnetic resonance imaging for predicting outcome following chemoradiotherapy, in squamous cell carcinomas of the anus.
Presenter: Rebecca Muirhead
Session: Poster Display session 2
Resources:
Abstract